1. Field of the invention
The present invention relates to a novel human myelomonocyte interferon-gamma, a process to prepare said interferon-gamma, and its use.
More particularly, the present invention relates to a novel human myelomonocyte interferon-gamma, and a process for preparing said interferon-gamma, characterized by allowing an established human myelomonocyte capable of producing myelomonocyte interferon-gamma to produce said interferon-gamma, and recovering the accumulation; a process to prepare a monoclonal anti-interferon-gamma antibody using the same; and a method for purifying said interferon-gamma using the monoclonal antibody, as well as to a prophylactic and therapeutic agent for interferon-gamma susceptive disease containing the human myelomonocyte interferon-gamma as an effective ingredient.
2. Description of the prior art
As described in Shigeyasu Kobayashi, "Interferon", published by Kodansha Co., Ltd., Tokyo, Japan (1975), D. A. J. Tyrrell, "Interferon and its Clinical Potential", published by William Heinemann Medical Books Ltd., London (1976), and Protein, Nucleic Acid and Enzyme, Vol. 21, No. 4, pp. 245-333 (1976), interferon is a name to designate glycoproteins that are extracellularly inducible in viable cell by subjecting it to the action of an interferon inducer, for example, virus, bacterium, protozoon, rickettsia, nucleic acid, endotoxin and polysaccharide, as well as having an activity of nonspecifically inhibiting viral growth.
This activity has rendered interferons since the discovery a potential prophylactic and therapeutic agent for viral diseases. Recent studies revealed that interferons exert an antioncotic activity on viral tumors, as well as on nonviral tumors. Because of the activity, the development of pharmaceuticals using interferons is in great expectation.
Interferons include interferon-alpha (or leukocyte interferon), interferon-beta (or fibroblast interferon), and interferon-gamma (or immune interferon). Preparation of interferon-alpha and interferon-beta has been established by using leukocyte and fibroblast cell. Recently, pharmaceuticals incorporated with these interferons have been commercialized.
Respective interferon will hereinafter be abbreviated as "IFN-alpha", "IFN-beta" and "IFN-gamma" occasionally with the prefix "Hu" representing human origin.
Although various methods have been proposed for preparing HuIFN-gamma, no method has been practiced on industrial scale.
The methods using leukocyte or T lymphocyte derived from human peripheral blood, as proposed, for example, in Japanese Patent Laid-Open Nos.58,891/82, 82,092/84, 70,099/85, 87,300/85, 139,700/85 and 149,600/85, International Patent Publication in Japanese Nos. 500,961/82 and 502,032/83, are practically unfavorable because an ample supply of the material cell is very difficult and the HuIFN producibility of these cells is insufficient.
Japanese Patent Laid-Open No.98,118/80 proposes the method wherein a human cell, obtained by implanting an established human cell in a non-human warm-blooded animal or placing the cell in a diffusion chamber provided inside or outside the body of a non-human warm-blooded animal, and allowing the cell to proliferate while allowing the cell to receive the nutrient body fluid from the animal, is used in preparing HuIFN-gamma. This method is characterized by an ample supply of the material human cell.
We found that the HuIFN-gamma productivity of the method varies with the type of the human cell used. Thus, the method has room for improvement in preparing consistently high-titered HuIFN-gamma to be practiceable on an industrial scale.
It is known that HuIFN-gamma is much more stronger in cytostatic and antioncotic activities than HuIFN-alpha and HuIFN-beta. Also is known that combination with HuIFN-alpha and/or HuIFN-beta augments the antiviral, cytostatic and antioncotic activities of HuIFN-gamma. For these reasons, development of an industrial-scale preparation of HuIFN-gamma has been in great demand.